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Gene Therapy for Prostate Cancer
Gene Therapy for Prostate Cancer Gene therapy is the use of DNA as a drug in the treatment of disease. This involves introducing DNA into a host that encodes a functional or therapeutic gene that will replace the harmful, mutated gene. Another option is introducing DNA that encodes a therapeutic protein drug or that directly corrects a mutation. If the therapeutic protein rout is taken, the DNA encoding the protein is put into a vector that will enter the damaged cells. Once inside, the cells own machinery will transcribe and translate the new DNA, producing the therapeutic protein itself. Another type of gene therapy in use today is suicide gene therapy. This involves introducing a vector containing a protein that will induce apoptosis in targeted cells. This strategy along with a few others has been very successful in the treatment of many cancers, including cancer of the prostate. p53 and p21 Cancer is uncontrolled growth of cells due to mutations in growth suppressing genes. p53 and p21 are both genes that suppress the growth of tumorous cells in humans. This is done by regulation of cell cycle. Normal p53 ''genes will induce apoptosis in mutated cells in the G1 checkpoint of the cell cycle. ''p21 is a gene that comes into play at the G1 checkpoint. Mutations in p53 will lead to a disfunction of the p21 gene that encodes proteins that aid in stopping cell growth. It has been discovered that p53 ''is the most commonly mutated gene in cases of human cancer. Furthermore, studies have shown that cell cycle arrest of ''p53 may function through actions of p21. Previous studies showed that the introduction of viral-mediated p53 suppresses the growth of a number of human cancer cells. However, a study conducted in 1995 comparing the uses of suicide gene therapy of p53 and p21 showed that p21 was much more successful in suppressing the growth of human cancer cells. Suicide Gene Therapy for Prostate Cancer Using p53 and p21 Adenoviruses The study was conducted using knock-out mice lacking the p53 gene. Recombinant adenovirus were constructed using a CMV promoter, wild-type human p53 or human '' p21'' cDNA and the SV40 polyadenylation signal that was inserted into a modified Ad5 vector with an E1-deletion. The resultant viruses were dubbed Ad5CMV-p53 and Ad5CMV-p21. Both adenoviruses were plated with mouse prostate cancer cells from the knock-out mice that were left to grow. Every 36-40 hours cells were harvested to keep stock of the progress p53 ''and p21'' were making. After the growth periods had elapsed, the results were collected and the following conclusions made. Although Ad5CMV-p53, the adenovirus containing the p53 gene that had previously been used in suicide gene therapy for prostate cancer, did indeed suppress growth of cancerous cells, it was not quite as successful as the p21 gene. Introduction of the p21 showed significant suppression of the growth of prostate cancer cells through apoptosis. Whereas Ad5CMV-p53 showed about a two fold decrease in cancerous cell growth, Ad5CMV-p21 reduced the rate of rumor growth by ~60% and significantly increased survival. References James A. Eastham, S. J. H., Inder Sehgal, et al. . (1995). In Vivo Gene Therapy with '' p53'' or '' p21'' Adenovirus for Prostate Cancer Cancer Research 55, 5151-5155.